Developments of gene expression systems that are controllable by external stimuli are attempted with the purpose of functional analyses or the like, of cellular proteins.
Japanese National-phase PCT Laid-Open Patent Publication No. 11-506901 discloses a transcription activator and a transcription inhibitor fusion protein that can control the expression of a gene linked to one or more tet operators. It is reported that, according to the transcription activator disclosed in Japanese National-phase PCT Laid-Open Patent Publication No. 11-506901, a control is possible in such a way that when tetracycline is present, the fusion protein binds a tet operator and transcription of the gene linked to the tet operator is stimulated, while in the absence of tetracycline, there is no binding or the like (therefore, there is no stimulation of transcription).
STANKUNAS K et al., “Conditional protein alleles using knockin mice and a chemical inducer of dimerization”, Mol. Cell., 2003, Vol. 12, No. 6, p. 1615-24 discloses the fusion protein GSK-3β FRB* of an 89 amino acid domain FRB*, which is the smallest region of FRAP (i.e., FKBP12-rapamycin binding protein) required for FKBP-12 rapamycin binding, and GSK-3β (i.e., endogenous glycogen synthase kinase-3β). STANKUNAS K et al state that FRB* triggers destabilization of GSK-3β, in other words, GSK-3β is destabilized by fusion with FRB* and degraded. In addition, STANKUNAS K et al describe that GSK-3β FRB* binds to FKBP12 in the presence of a rapamycin derivative (C20-MaRap), and that this interaction stabilizes GSK-3β FRB*. The system by STANKUNAS K et al is described as one that promotes dimerization between FKB* and FKBP12 by the sole use of a rapamycin derivative.